HER2 (also called ErbB2) is a receptor-type tyrosine kinase belonging to the ErbB family.
HER2 is considered as a gene responsible for cancer (Non Patent Literature 1), and HER2 gene amplification, mutation, overexpression, and the like have been reported on various cancers (Non Patent Literature 2). It has been reported that the survival, growth signals, etc. of the cancer cells are increased by the activation of the signal transmission of HER2 and its downstream pathway in cancer cells having such HER2 gene abnormality or overexpression (Non Patent Literatures 3 and 4).
Thus, an inhibitor capable of controlling the kinase activity of HER2 presumably exerts antitumor effect by inhibiting the signal transduction of HER2 and its downstream pathway in cancer cells, and is therefore considered to be useful as a therapeutic drug for cancer.
Lapatinib (Non Patent Literature 5), afatinib (Non Patent Literature 6), and neratinib (Non Patent Literature 7) are known as compounds having HER2 inhibitory activity. These three compounds are known to exhibit high inhibitory activity against EGFR (epidermal growth factor receptor), in addition to HER2. However, such compounds might cause adverse effects due to the inhibition of the signaling pathway of EGFR. For example, inhibitors targeting EGFR are known to commonly cause adverse effects such as skin problems and gastrointestinal tract disturbances, and these adverse effects seem to be associated with the inhibition of the wild-type EGFR signaling pathway (Non Patent Literatures 8, 9, and 10).
Therefore, from the viewpoint of reducing adverse effects, there has been a demand for a highly selective HER2 inhibitor which has high inhibitory activity against HER2, but has low inhibitory activity against other kinases such as EGFR.